Overall Survival Benefit with Ribociclib plus Endocrine Therapy in Patients with Hormone Receptor–Positive, HER2-Negative Advanced Breast Cancer: 4-Year Follow-Up Study of MONALEESA-7

Updated overall survival results from the phase 3 MONALEESA-7 trial show that in a 4-year extended follow-up study of pre- and perimenopausal patients with hormone receptor–positive, HER2-negative advanced breast cancer, ribociclib plus endocrine therapy exhibited a clinically relevant overall survival benefit.

In 2019, results of the MONALEESA-7 clinical trial were published in the New England Journal of Medicine as the first large, randomized, phase 3 trial that focused on investigating in pre- or perimenopausal patients with hormone receptor–positive, HER2-negative advanced breast cancer comparing a CDK4/6 inhibitor plus endocrine therapy with placebo plus endocrine therapy. The study showed a statistically significant improvement in overall survival when ribociclib was given in combination with endocrine therapy compared with placebo plus endocrine therapy. The median overall survival could not be estimated in the ribociclib group and was 40.9 months in the placebo group (95% confidence interval [CI], 0.54-0.95; P = .00973).¹ Unblinding to treatment assignment allowed patients who received placebo to cross over to ribociclib treatment, following the conclusion of the final analysis of overall survival.

Allowing for lengthier follow-up helps to provide a more accurate characterization of long-term survival benefits by expanding the window for possible events. The results of an exploratory update on overall survival after a minimum of approximately 4 years of follow-up and an additional 20 months since the last report were reported by Debasish Tripathy, MD, Professor and Chairman, Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston.

Ribociclib has received US Food and Drug Administration approval to treat in pre- or perimenopausal patients in combination with a nonsteroidal aromatase inhibitor.

Patients with hormone receptor–positive, HER2-negative advanced breast cancer who were pre- and perimenopausal were randomized 1:1 to receive ribociclib or placebo plus goserelin, with either a nonsteroidal aromatase inhibitor (letrozole or anastrozole) or tamoxifen. The study excluded patients who had been treated previously with a CDK4/6 inhibitor or endocrine therapy in the advanced setting. However, the study did enroll recipients of endocrine therapy in the neoadjuvant setting or those who have had ≤1 previous lines of chemotherapy for advanced disease. Time to chemotherapy, chemotherapy-free survival, and time to second objective disease progression (PFS2) were also assessed.

For the updated overall survival analysis, the data cutoff was June 29, 2020. The median follow-up was 53.5 months (minimum, 46.9 months). The updated findings with continued follow-up showed a benefit to overall survival with ribociclib plus endocrine therapy compared with placebo plus endocrine therapy (median, 58.7 vs 48.0 months; hazard ratio [HR], 0.76; 95% CI, 0.61-0.96). In patients who received a nonsteroidal aromatase inhibitor, a similar benefit to overall survival was observed, with ribociclib plus nonsteroidal aromatase inhibitor compared with nonsteroidal aromatase inhibitor (median, 58.7 vs 47.7 months; HR, 0.80; 95% CI, 0.62-1.04).

Consistent with outcomes in the intent-to-treat population were the subgroup analyses, with respect to survival benefit. Benefit with ribociclib was observed with regard to PFS2, time to chemotherapy, and chemotherapy-free survival compared with the nonsteroidal aromatase inhibitor cohort.

Of those patients who discontinued treatment in the study, 77.3% in the ribociclib plus endocrine therapy arm and 78.1% in the placebo plus endocrine therapy arm received a subsequent antineoplastic treatment, and 12.9% and 26.1% received a subsequent line of CDK4/6 inhibitor, respectively. Furthermore, 15 patients in the placebo arm crossed over to receive ribociclib after undergoing unblinding and before progression of the disease.

Based on a more than 4-year extended follow-up study of pre- and perimenopausal patients with hormone receptor–positive, HER2-negative advanced breast cancer, ribociclib plus endocrine therapy exhibited a clinically relevant overall survival benefit when compared with endocrine therapy alone. In this population, the median overall survival was approximately 5 years with ribociclib plus endocrine therapy treatment. With ribociclib, the benefit was comparable with respect to PFS2, chemotherapy-free survival, and time to chemotherapy.

Source: Tripathy D, Im SA, Colleoni M, et al. Updated overall survival (OS) results from the phase III MONALEESA-7 trial of pre- or perimenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PD2-04.

Reference
1. Im S-A, Lu Y-S, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019;381:307-316.